Systematic analysis of SCN5A variants associated with inherited cardiac diseases.

BACKGROUND: SCN5A variants are associated with a spectrum of cardiac electrical disorders with clear phenotypes. However, they may also be associated with complex phenotypic traits like overlap syndromes, or pleiotropy, which have not been systematically described. Additionally, the involvement of SCN5A in dilated cardiomyopathies (DCM) remains controversial. OBJECTIVE: We aimed to (1) evaluate the different phenotypes associated with pathogenic (P)/likely pathogenic (LP) SCN5A variants and (2) determine the prevalence of pleiotropy in a large multicentric cohort of P/LP SCN5A variant carriers. METHODS: The DNA of 13,510 consecutive probands (9960 with cardiomyopathies) was sequenced using a custom panel of genes. Individuals carrying a heterozygous single P/LP SCN5A variant were selected and phenotyped. RESULTS: The study included 170 P/LP variants found in 495 patients. Among them, 119 (70%) were exclusively associated with a single well-established phenotype: 91 with Brugada syndrome, 15 with type 3 long QT syndrome, six with progressive cardiac conduction disease, four with multifocal ectopic Purkinje-related premature contraction, and three with sick sinus syndrome. Thirty-two variants (19%) were associated with overlap syndromes and/or pleiotropy. The 19 remaining variants (11%) were associated with atypical or unclear phenotypes. Among those, eight were carried by eight patients presenting with DCM with a debatable causative genotype/phenotype link. CONCLUSION: Most P/LP SCN5A variants were found in patients with primary electrical disorders, mainly Brugada syndrome. Nearly 20% were associated with overlap syndromes or pleiotropy, underscoring the need for comprehensive phenotypic evaluation. The concept of SCN5A variants causing DCM is extremely rare (8/9960), if not questionable.

Norepinephrine weaning guided by the Hypotension Prediction Index in vasoplegic shock after cardiac surgery: protocol for a single-centre, open-label randomised controlled trial - the NORAHPI study.

INTRODUCTION: Norepinephrine (NE) is the first-line recommended vasopressor for restoring mean arterial pressure (MAP) in vasoplegic syndrome (vs) following cardiac surgery with cardiopulmonary bypass. However, solely focusing on target MAP values can lead to acute hypotension episodes during NE weaning. The Hypotension Prediction Index (HPI) is a machine learning algorithm embedded in the Acumen IQ device, capable of detecting hypotensive episodes before their clinical manifestation. This study evaluates the clinical benefits of an NE weaning strategy guided by the HPI. MATERIAL AND ANALYSIS: The Norahpi trial is a prospective, open-label, single-centre study that randomises 142 patients. Inclusion criteria encompass adult patients scheduled for on-pump cardiac surgery with postsurgical NE administration for vs patient randomisation occurs once they achieve haemodynamic stability (MAP>65 mm Hg) for at least 4 hours on NE. Patients will be allocated to the intervention group (n=71) or the control group (n=71). In the intervention group, the NE weaning protocol is based on MAP>65 mmHg and HPI<80 and solely on MAP>65 mm Hg in the control group. Successful NE weaning is defined as achieving NE weaning within 72 hours of inclusion. An intention-to-treat analysis will be performed. The primary endpoint will compare the duration of NE administration between the two groups. The secondary endpoints will include the prevalence, frequency and time of arterial hypotensive events monitored by the Acumen IQ device. Additionally, we will assess cumulative diuresis, the total dose of NE, and the number of protocol weaning failures. We also aim to evaluate the occurrence of postoperative complications, the length of stay and all-cause mortality at 30 days. ETHICS AND DISSEMINATION: Ethical approval has been secured from the Institutional Review Board (IRB) at the University Hospital of Amiens (IRB-ID:2023-A01058-37). The findings will be shared through peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05922982.

Successful removal of an intra-pericardic Kirschner wire via fluoroscopy-guided minimal invasive approach: a case report.

BACKGROUND: Kirschner wires are widely used in trauma surgery. Their migration into the pericardium is a rare but often fatal phenomenon, requiring urgent management. CASE PRESENTATION: We describe the case of a 65-year-old patient who underwent Kirschner wire placement to treat a humeral head fracture. Three months after the operation, pleural and pericardial effusions with cardiac tamponade were observed, leading to the diagnosis of wire migration within the pericardium. A minimally invasive approach guided by fluoroscopy allowed emergency wire extraction without needing a median sternotomy. The postoperative clinical course was uncomplicated. CONCLUSIONS: The use of pre- and per-operative multimodal imaging allowed for the safe extraction of an intra-pericardial Kirschner wire through a minimally invasive approach.

Prognostic Value of a New Right Ventricular-to-Pulmonary Artery Coupling Parameter Using Right Ventricular Longitudinal Shortening Fraction in Patients Undergoing Transcatheter Aortic Valve Replacement: A Prospective Echocardiography Study.

Introduction: Right-ventricular-to-pulmonary artery (RV-PA) coupling, measured as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP), has emerged as a predictor factor in patients undergoing transcatheter aortic valvular replacement (TAVR). Right ventricular longitudinal shortening fraction (RV-LSF) outperformed TAPSE as a prognostic parameter in several diseases. We aimed to compare the prognostic ability of two RV-PA coupling parameters (TAPSE/PASP and the RV-LSF/PASP ratio) in identifying MACE occurrences. Method: A prospective and single-center study involving 197 patients who underwent TAVR was conducted. MACE (heart failure, myocardial infarction, stroke, and death within six months) constituted the primary outcome. ROC curve analysis determined cutoff values for RV-PA ratios. Multivariable Cox regression analysis explored the association between RV-PA ratios and MACE. Results: Forty-six patients (23%) experienced the primary outcome. No significant difference in ROC curve analysis was found (RV-LSF/PASP with AUC = 0.67, 95%CI = [0.58-0.77] vs. TAPSE/PASP with AUC = 0.62, 95%CI = [0.49-0.69]; p = 0.16). RV-LSF/PASP < 0.30%.mmHg-1 was independently associated with the primary outcome. The 6-month cumulative risk of MACE was 59% (95%CI = [38-74]) for patients with RV-LSF/PASP < 0.30%.mmHg-1 and 17% (95%CI = [12-23]) for those with RV-LSF/PASP ≥ 0.30%.mmHg-1; (p < 0.0001). Conclusions: In a contemporary cohort of patients undergoing TAVR, RV-PA uncoupling defined by an RV-LSF/PASP < 0.30%.mmHg-1 was associated with MACE at 6 months.

Left atrial strain analysis and new-onset atrial fibrillation in patients with ST-segment elevation myocardial infarction: A prospective echocardiography study.

BACKGROUND: New-onset atrial fibrillation (NOAF) is a well-known complication of ST-segment elevation myocardial infarction (STEMI), probably due to left atrial (LA) remodelling. LA strain (LAS) can predict NOAF in several cardiovascular diseases. OBJECTIVE: To assess whether LAS predicts NOAF in sinus rhythm patients with STEMI during hospitalization. METHODS: Adults with a STEMI and transthoracic echocardiography performed within 48hours of admission were included. LAS analysis, performed by automated software, recorded LAS during the reservoir phase (LASr), the conduit phase (LAScd) and the contraction phase (LASct). RESULTS: From May 2021 to November 2022, 175 patients were included, 21 (12%) of whom developed NOAF. NOAF patients were older (median [Q1-Q3]: 67 [59-80] vs 59 [51-67]years; P=0.006) and had a higher Thrombolysis In Myocardial Infarction scores (4 [2-7] vs 3 [1-4]; P=0.005). All LAS parameters were significantly impaired in NOAF patients, especially LASr (13.0% [10.5-28.4] vs 36.6% [29.0-44.9]; P=0.001). An LASr cut-off of 27% had a sensitivity of 81% and a specificity of 80% to identify patients with NOAF. In a multivariable model, LASr was significantly associated with NOAF (odds ratio 1.18, 95% confidence interval 1.09-1.26; P=0.003). The cumulative risk of NOAF during hospital stay was 30% (18-43 with LASr<27% and 4% [1.5-8.5] with LASr≥27% [P<0.0001]). CONCLUSION: NOAF is a frequent complication of STEMI. LASr seems helpful for identifying patients at high risk of NOAF during hospitalization.

Prognostic Value of Right Ventricular Longitudinal Shortening Fraction in Patients With ST-Elevation Myocardial Infarction: A Prospective Echocardiography Study.

Right ventricular systolic dysfunction (RVsD) frequently occurs in patients with ST-elevation myocardial infarction (STEMI). However, the diagnosis depends on the echocardiographic parameters to define RVsD. The right ventricle longitudinal shortening fraction (RV-LSF) is an accurate and reproducible 2-dimensional speckle-tracking parameter associated with clinical events in various pathologies. This study aimed to evaluate the association between RVsD and major adverse cardiovascular event (MACE) occurrence in a cohort of patients with STEMI. Adult patients with STEMI admitted to Amiens University Hospital's cardiovascular intensive care unit between May 2021 and November 2022 who underwent coronary angiography and transthoracic echocardiography within 48 hours of admission were included. RVsD was defined as RV-LSF <20%. The primary outcome was MACE occurrence, including heart failure, myocardial infarction, stroke, and death within 6 months of admission. A multivariable Cox regression analysis with proportional hazard ratio models assessed the association between RVsD and MACEs. In the 164 included patients, 72 (44%) had RVsD and 92 (56%) did not. The RVsD group had a significantly higher proportion of MACEs during the 6-month follow-up (n = 23 of 72, 33%) than the group without RVsD (n = 8 of 92, 9%, p = 0.001). RVsD showed an independent association with MACEs at 6 months (hazard ratio 3.1, 95% confidence interval [CI] 1.35 to 7.30, p = 0.008). Left ventricular ejection fraction <40% and Thrombolysis in Myocardial Infarction score >4 were independently associated with RVsD (odds ratio 2.80, 95% CI 1.34 to 5.98 and odds ratio 2.15, 95% CI 1.18 to 4.39, respectively, p = 0.015). The cumulative risk of MACEs at 6 months was 33% for RV-LSF <20% and 9% for RV-LSF ≥20% (log-rank test p <0.001). RVsD, defined by RV-LSF <20%, is associated with an increased risk of MACEs after STEMI.

Prognostic value of right ventricular dilatation on computed tomography pulmonary angiogram for predicting adverse clinical events in severe COVID-19 pneumonia.

Background: Right ventricle dilatation (RVD) is a common complication of non-intubated COVID-19 pneumonia caused by pro-thrombotic pneumonitis, intra-pulmonary shunting, and pulmonary vascular dysfunction. In several pulmonary diseases, RVD is routinely measured on computed tomography pulmonary angiogram (CTPA) by the right ventricle-to-left ventricle (LV) diameter ratio > 1 for predicting adverse events. Objective: The aim of the study was to evaluate the association between RVD and the occurrence of adverse events in a cohort of critically ill non-intubated COVID-19 patients. Methods: Between February 2020 and February 2022, non-intubated patients admitted to the Amiens University Hospital intensive care unit for COVID-19 pneumonia with CTPA performed within 48 h of admission were included. RVD was defined by an RV/LV diameter ratio greater than one measured on CTPA. The primary outcome was the occurrence of an adverse event (renal replacement therapy, extracorporeal membrane oxygenation, 30-day mortality after ICU admission). Results: Among 181 patients, 62% (n = 112/181) presented RVD. The RV/LV ratio was 1.10 [1.05-1.18] in the RVD group and 0.88 [0.84-0.96] in the non-RVD group (p = 0.001). Adverse clinical events were 30% and identical in the two groups (p = 0.73). In Receiving operative curves (ROC) analysis, the RV/LV ratio measurement failed to identify patients with adverse events. On multivariable Cox analysis, RVD was not associated with adverse events to the contrary to chest tomography severity score > 10 (hazards ratio = 1.70, 95% CI [1.03-2.94]; p = 0.04) and cardiovascular component (> 2) of the SOFA score (HR = 2.93, 95% CI [1.44-5.95], p = 0.003). Conclusion: Right ventricle (RV) dilatation assessed by RV/LV ratio was a common CTPA finding in non-intubated critical patients with COVID-19 pneumonia and was not associated with the occurrence of clinical adverse events.

Two-year prognosis of acute coronary syndrome during the first wave of the coronavirus disease 2019 pandemic.

BACKGROUND: The first wave of the coronavirus disease 2019 pandemic significantly changed behaviour in terms of access to healthcare. AIM: To assess the effects of the pandemic and initial lockdown on the incidence of acute coronary syndrome and its long-term prognosis. METHODS: Patients admitted for acute coronary syndrome from 17 March to 6 July 2020 and from 17 March to 6 July 2019 were included. The number of admissions for acute coronary syndrome, acute complication rates and 2-year rates of survival free from major adverse cardiovascular events or death from any cause were compared according to the period of hospitalization. RESULTS: In total, 289 patients were included. We observed a 30±3% drop in acute coronary syndrome admissions during the first lockdown, which did not recover in the 2months after it was lifted. At 2years, there were no significant differences in the combined endpoint of major adverse cardiovascular events or death from any cause between the different periods (P=0.34). Being hospitalized during lockdown was not predictive of adverse events during follow-up (hazard ratio 0.87, 95% confidence interval 0.45-1.66; P=0.67). CONCLUSIONS: We did not observe an increased risk of major cardiovascular events or death at 2years from initial hospitalization for patients hospitalized during the first lockdown, adopted in March 2020 in response to the coronavirus disease 2019 pandemic, potentially as a result of the lack of power of the study.

Prognostic value of acute cor pulmonale in COVID-19-related pneumonia: A prospective study.

Background: It is known that acute cor pulmonale (ACP) worsens the prognosis of non-coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (NC-ARDS). The ACP risk score evaluates the risk of ACP occurrence in mechanically ventilated patients with NC-ARDS. There is less data on the risk factors and prognosis of ACP induced by COVID-19-related pneumonia. Objective: The objective of this study was to evaluate the prognostic value of ACP, assessed by transthoracic echocardiography (TTE) and clinical factors associated with ACP in a cohort of patients with COVID-19-related pneumonia. Materials and methods: Between February 2020 and June 2021, patients admitted to intensive care unit (ICU) at Amiens University Hospital for COVID-19-related pneumonia were assessed by TTE within 48 h of admission. ACP was defined as a right ventricle/left ventricle area ratio of >0.6 associated with septal dyskinesia. The primary outcome was mortality at 30 days. Results: Among 146 patients included, 36% (n = 52/156) developed ACP of which 38% (n = 20/52) were non-intubated patients. The classical risk factors of ACP (found in NC-ARDS) such as PaCO2 >48 mmHg, driving pressure >18 mmHg, and PaO2/FiO2 < 150 mmHg were not associated with ACP (all P-values > 0.1). The primary outcome occurred in 32 (22%) patients. More patients died in the ACP group (n = 20/52 (38%) vs. n = 12/94 (13%), P = 0.001). ACP [hazards ratio (HR) = 3.35, 95%CI [1.56-7.18], P = 0.002] and age >65 years (HR = 2.92, 95%CI [1.50-5.66], P = 0.002) were independent risk factors of 30-day mortality. Conclusion: ACP was a frequent complication in ICU patients admitted for COVID-19-related pneumonia. The 30-day-mortality was 38% in these patients. In COVID-19-related pneumonia, the classical risk factors of ACP did not seem relevant. These results need confirmation in further studies.

Mortality of COVID-19 Patients Requiring Extracorporeal Membrane Oxygenation During the Three Epidemic Waves.

Clinical presentation and mortality of patients treated with extracorporeal membrane oxygenation (ECMO) for COVID-19 acute respiratory distress syndrome (CARDS) were different during the French epidemic waves. The management of COVID-19 patients evolved through waves as much as knowledge on that new viral disease progressed. We aimed to compare the mortality rate through the first three waves of CARDS patients on ECMO and identify associated risk factors. Fifty-four consecutive ECMO for CARDS hospitalized at Amiens University Hospital during the three waves were included. Patients were divided into three groups according to their hospitalization date. Clinical characteristics and outcomes were compared between groups. Pre-ECMO risk factors predicting 90 day mortality were evaluated using multivariate Cox regression. Among 54 ECMO (median age of 61[48-65] years), 26% were hospitalized during the first wave (n = 14/54), 26% (n = 14/54) during the second wave, and 48% (n = 26/54) during the third wave. Time from first symptoms to ECMO was higher during the second wave than the first wave. (17 [12-23] days vs. 11 [9-15]; p < 0.05). Ninety day mortality was higher during the second wave (85% vs. 43%; p < 0.05) but less during the third wave (38% vs. 85%; P < 0.05). Respiratory ECMO survival prediction score and time from symptoms onset to ECMO (HR 1.12; 95% confidence interval [CI]: 1.05-1.20; p < 0.001) were independent factors of mortality. After adjustment, time from symptoms onset to ECMO was an independent factor of 90 day mortality. Changes in CARDS management from first to second wave-induced a later ECMO cannulation from symptoms onset with higher mortality during that wave. The duration of COVID-19 disease progression could be selection criteria for initiating ECMO.

Early hyperoxia and 28-day mortality in patients on venoarterial ECMO support for refractory cardiogenic shock: a bicenter retrospective propensity score-weighted analysis.

BACKGROUND: The mortality rate for a patient with a refractory cardiogenic shock on venoarterial (VA) extracorporeal membrane oxygenation (ECMO) remains high, and hyperoxia might worsen this prognosis. The objective of the present study was to evaluate the association between hyperoxia and 28-day mortality in this setting. METHODS: We conducted a retrospective bicenter study in two French academic centers. The study population comprised adult patients admitted for refractory cardiogenic shock. The following arterial partial pressure of oxygen (PaO2) variables were recorded for 48 h following admission: the absolute peak PaO2 (the single highest value measured during the 48 h), the mean daily peak PaO2 (the mean of each day's peak values), the overall mean PaO2 (the mean of all values over 48 h), and the severity of hyperoxia (mild: PaO2 < 200 mmHg, moderate: PaO2 = 200-299 mmHg, severe: PaO2 ≥ 300 mmHg). The main outcome was the 28-day all-cause mortality. Inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalances in baseline characteristics. RESULTS: From January 2013 to January 2020, 430 patients were included and assessed. The 28-day mortality rate was 43%. The mean daily peak, absolute peak, and overall mean PaO2 values were significantly higher in non-survivors than in survivors. In a multivariate logistic regression analysis, the mean daily peak PaO2, absolute peak PaO2, and overall mean PaO2 were independent predictors of 28-day mortality (adjusted odds ratio [95% confidence interval per 10 mmHg increment: 2.65 [1.79-6.07], 2.36 [1.67-4.82], and 2.85 [1.12-7.37], respectively). After IPW, high level of oxygen remained significantly associated with 28-day mortality (OR = 1.41 [1.01-2.08]; P = 0.041). CONCLUSIONS: High oxygen levels were associated with 28-day mortality in patients on VA-ECMO support for refractory cardiogenic shock. Our results confirm the need for large randomized controlled trials on this topic.

Association between acute kidney injury and norepinephrine use following cardiac surgery: a retrospective propensity score-weighted analysis.

BACKGROUND: Excess exposure to norepinephrine can compromise microcirculation and organ function. We aimed to assess the association between norepinephrine exposure and acute kidney injury (AKI) and intensive care unit (ICU) mortality after cardiac surgery. METHODS: This retrospective observational study included adult patients who underwent cardiac surgery under cardiopulmonary bypass from January 1, 2008, to December 31, 2017, at the Amiens University Hospital in France. The primary exposure variable was postoperative norepinephrine during the ICU stay and the primary endpoint was the presence of AKI. The secondary endpoint was in-ICU mortality. As the cohort was nonrandom, inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalances in the pre- and intra-operative characteristics. RESULTS: Among a population of 5053 patients, 1605 (32%) were exposed to norepinephrine following cardiac surgery. Before weighting, the prevalence of AKI was 25% and ICU mortality 10% for patients exposed to norepinephrine. Exposure to norepinephrine was estimated to be significantly associated with AKI by a factor of 1.95 (95% confidence interval, 1.63-2.34%; P < 0.001) in the IPW cohort and with in-ICU mortality by a factor of 1.54 (95% confidence interval, 1.19-1.99%; P < 0.001). CONCLUSION: Norepinephrine was associated with AKI and in-ICU mortality following cardiac surgery. While these results discourage norepinephrine use for vasoplegic syndrome in cardiac surgery, prospective investigations are needed to substantiate findings and to suggest alternative strategies for organ protection.

Feasibility, Prediction and Association of Right Ventricular Free Wall Longitudinal Strain with 30-Day Mortality in Severe COVID-19 Pneumonia: A Prospective Study.

Introduction: Right ventricular (RV) systolic dysfunction (RVsD) is a common complication of coronavirus infection 2019 disease (COVID-19). The right ventricular free wall longitudinal strain parameter (RV-FWLS) is a powerful predictor of mortality. We explored the performance of RVsD parameters for predicting 30-day mortality and the association between RV-FWLS and 30-day mortality. Methods: COVID-19 patients hospitalized at Amiens University Hospital in the critical care unit with transthoracic echocardiography were included. We measured tricuspid annular plane systolic excursion (TAPSE), the RV S' wave, RV fractional area change (RV-FAC), and RV-FWLS. The diagnostic performance of RVsD parameters as predictors for 30-day mortality was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). RVsD was defined by an RV-FWLS < 21% to explore the association between RVsD and 30-day mortality. Results: Of the 116 patients included, 20% (n = 23/116) died and 47 had a RVsD. ROC curve analysis showed that RV-FWLS failed to predict 30-day mortality, as did conventional RV parameters (all p > 0.05). TAPSE (21 (19−26) mm vs. 24 (21−27) mm; p = 0.024) and RV-FAC (40 (35−47)% vs. 47 (41−55)%; p = 0.006) were lowered in the RVsD group. In Cox analysis, RVsD was not associated with 30-day mortality (hazard ratio = 1.12, CI 95% (0.49−2.55), p = 0.78). Conclusion: In severe COVID-19 pneumonia, RV-FWLS was not associated with 30-day mortality.

Sex Differences in the Outcomes of Cryoablation for Atrial Fibrillation.

Background: The literature data on the outcomes of radiofrequency catheter ablation for atrial fibrillation (AF) in women are contradictory. Aim: To determine and compare the outcomes and complications of cryoballoon pulmonary vein isolation (cryo-PVI) in men vs. women, and to identify predictors of atrial tachyarrhythmia (ATa) recurrence. Methods: We included all consecutive patients having undergone cryo-PVI for the treatment of symptomatic AF in our center since 2012. Peri-operative complications were documented. All patients were prospectively monitored for the recurrence of ATa, and predictors were assessed. Results: A total of 733 patients were included (550 men (75%) and 183 (25%) women). Paroxysmal AF was recorded in 112 (61%) female patients and 252 male patients (46%; p < 0.001). Female patients were older (p < 0.001) and had a greater symptom burden (p = 0.04). Female patients were more likely to experience complications (p = 0.02). After cryo-PVI for paroxysmal AF, 66% of the female patients and 79% of the male patients were free of ATa at 24 months (p = 0.001). Female sex was the only independent predictive factor for ATa recurrence (hazard ratio [95% confidence interval] = 1.87 [1.28; 2.73]; p = 0.001). After cryo-PVI for non-paroxysmal AF, 37% of the male patients and 39% of the female patients were free of ATa at 36 months (p = 0.73). Female patients were less likely than male patients to undergo repeat ablation after an index cryo-PVI for non-paroxysmal AF (p = 0.019). Conclusion: A single cryo-PVI procedure for paroxysmal AF was significantly less successful in female patients than in male patients. Overall, the complication rate was higher in women than in men.

Portal Vein Pulsatility Index as a Potential Risk of Venous Congestion Assessed by Magnetic Resonance Imaging: A Prospective Study on Healthy Volunteers.

High values of the portal vein pulsatility index (PI) have been associated with adverse outcomes in perioperative or critically ill patients. However, data on dynamic changes of PI related to fluid infusion are scarce. We aimed to determine if dynamic changes in PI are associated with the fluid challenge (FC). To address this challenge, we conducted a prospective single-center study. The population study included healthy subjects. FC consisted in the administration of 500 ml of Ringer lactate infusion over 5 min. The portal blood flow and PI were assessed by magnetic resonance imaging. The responsiveness to FC was defined as an increase in the cardiac stroke volume of at least 10% as assessed by echocardiography. We included 24 healthy volunteers. A total of fourteen (58%) subjects were responders, and 10 (42%) were non-responders. In the responder group, FC induced a significant increase in portal blood flow from 881 (762-1,001) at the baseline to 1,010 (778-1,106) ml min-1 (p = 0.005), whilst PI remained stable (from 31 [25-41] to 35 (25-42) %; p = 0.12). In the non-responder group, portal blood flow remained stable after FC (from 1,042 to 1,034 ml min-1; p = 0.084), whereas PI significantly increased from 32 (22-40) to 48% *(25-85) after FC (p = 0.027). PI was negatively correlated to portal blood flow (Rho coefficient = -0.611; p = 0.002). To conclude, PI might be a sensitive marker of early congestion in healthy subjects that did not respond to FC. This finding requires further validation in clinical settings with a larger sample size.